Background/Aims: In order to clarify an appropriate intake of docosahexaenoic acid (DHA, 22:6n–3), from the viewpoint of safety and physiological efficacy, the potential changes in lipid peroxidation and antioxidant defense in serum and tissues as well as those in serum lipid levels were examined in matured rats at the age of 1 year. Methods: Rats were given the diets containing graded levels of purified DHA (0, 1.0, 3.1 and 8.4% of total energy, en%) for 30 days (control and 1.0, 3.1 and 8.4 en% groups). Lipid peroxides and α-tocopherol levels in serum and tissues, and lipid levels in serum were measured. Results: Serum α-tocopherol concentrations in the 3.1 and 8.4 en% groups were significantly lower than those in the control group. Liver lipid peroxide levels assessed using the microsomal conjugated dienes were significantly higher in the 3.1 and 8.4 en% groups than those in the control group, and the chemiluminescence intensity and thiobarbituric acid value were significantly greater in the 8.4 en% group than in the control group. The liver α-tocopherol level decreased in response to the increases in lipid peroxide levels, but a significant difference was recognized only in the 8.4 en% group. In the kidney, no changes in lipid peroxide levels were observed, but the α-tocopherol level was significantly lower in the 8.4 en% group than in the control group. The levels of all the serum lipids including total cholesterol, HDL-cholesterol, triacylglycerols and phospholipids decreased as the dietary DHA level increased, and total cholesterol and phospholipid concentrations were significantly lower in the 3.1 and 8.4 en% groups than in the control group. Conclusion: These experimental results suggest that the dietary intake of DHA should not be more than 3 en% in matured rats to avoid the potentially chronic deleterious influences caused by lipid peroxidation in serum and tissues, and that the amelioration of serum lipid levels is recognized in rats fed DHA at 3 en% and above.

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